Asthma and chronic obstructive pulmonary disease (COPD) are the two leading chronic respiratory diseases in the US. However, reliable in vitro human models are not widely available to pharmaceutical researchers who are attempting to understand asthma and COPD pathogenesis and develop therapeutic interventions for these diseases. The goal of the present grant proposal is to fulfill this unmet need by developing commercially available tissue engineered in vitro human models of asthma and COPD. These models will consist of well-differentiated 3-D cultures of human tracheal/bronchial epithelium as well as human airway epithelium co-cultured with human airway mesenchymal cells. Epithelial and mesenchymal cells isolated from diseased tissues will be utilized to produce the models. A cell bank initiated as a source for model production during Phase I will be expanded during Phase II and in future years, to build a larger inventory of cells and to replenish cells as they are utilized. Tissue engineered in vitro human models for asthma and COPD will provide important unique attributes that animal models cannot provide, including the ability to address human individual variability and genetic factors; a means to determine mechanisms of human virus elicitation of asthma and COPD exacerbations; and a higher throughput, economical means of asthma and COPD therapeutic development at the preclinical/pre-animal level. These models will provide pharmaceutical researchers important new tools for investigating the role of airway epithelium and mesenchymal cells in asthma and COPD pathogenesis and development and testing of new therapeutic treatments for these diseases. The goal of the present grant proposal is to develop commercially available tissue engineered in vitro human models of asthma and COPD. These models will consist of well-differentiated 3-D cultures of tracheal/bronchial epithelium as well as airway epithelium co-cultured with airway mesenchymal cells. Epithelial and mesenchymal cells isolated from diseased tissues will be utilized to produce the models. The models to be developed will provide pharmaceutical researchers important tools for investigating the role of airway epithelium and mesenchymal cells in asthma and COPD pathogenesis and development and testing of new therapeutic treatments for these diseases. [unreadable] [unreadable] [unreadable]